Ionophore Ability of Carnosine and Its Trehalose Conjugate Assists Copper Signal in Triggering Brain-Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Activation In Vitro.
Irina NaletovaValentina GrecoSebastiano SciutoFrancesco AttanasioEnrico RizzarelliPublished in: International journal of molecular sciences (2021)
l-carnosine (β-alanyl-l-histidine) (Car hereafter) is a natural dipeptide widely distributed in mammalian tissues and reaching high concentrations (0.7-2.0 mM) in the brain. The molecular features of the dipeptide underlie the antioxidant, anti-aggregating and metal chelating ability showed in a large number of physiological effects, while the biological mechanisms involved in the protective role found against several diseases cannot be explained on the basis of the above-mentioned properties alone, requiring further research efforts. It has been reported that l-carnosine increases the secretion and expression of various neurotrophic factors and affects copper homeostasis in nervous cells inducing Cu cellular uptake in keeping with the key metal-sensing system. Having in mind this l-carnosine ability, here we report the copper-binding and ionophore ability of l-carnosine to activate tyrosine kinase cascade pathways in PC12 cells and stimulate the expression of BDNF. Furthermore, the study was extended to verify the ability of the dipeptide to favor copper signaling inducing the expression of VEGF. Being aware that the potential protective action of l-carnosine is drastically hampered by its hydrolysis, we also report on the behavior of a conjugate of l-carnosine with trehalose that blocks the carnosinase degradative activity. Overall, our findings describe a copper tuning effect on the ability of l-carnosine and, particularly its conjugate, to activate tyrosine kinase cascade pathways.
Keyphrases
- tyrosine kinase
- vascular endothelial growth factor
- poor prognosis
- epidermal growth factor receptor
- oxide nanoparticles
- gene expression
- cancer therapy
- induced apoptosis
- endothelial cells
- oxidative stress
- long non coding rna
- signaling pathway
- drug delivery
- single molecule
- quality improvement
- cell proliferation
- climate change
- human health
- resting state
- subarachnoid hemorrhage
- pi k akt
- functional connectivity